4,6-dichloro-5-(2,2-diethoxyethyl)Pyrimidine

64-17-5

16019-33-3

14052-82-5

Step 1: 4,6-Dichloropyrimidine-5-acetaldehyde (500.0 g, 2.618 mol) and ammonium chloride (14.0 g, 0.262 mol) were suspended in anhydrous ethanol (4.02 L, 68.9 mol). The suspension was heated to 85 °C and kept for the reaction, and the progress of the reaction was monitored by 1H NMR, with samples taken after the initial 2 h and every hour thereafter. After 5 hours of reaction, 1H NMR analysis showed that the reaction was essentially complete (~5% of the starting aldehyde remaining). The reaction mixture was cooled to room temperature, activated charcoal (80 g) was added and stirred for 10 min, then filtered through Celite 545. The filter bed was washed with anhydrous ethanol (500 mL). The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane (4.02 L) and the organic phase was washed sequentially with water (2.4 L) and brine (2.4 L). The organic phase was dried with anhydrous sodium sulfate, filtered through Celite 545, concentrated under reduced pressure, and then dried in a vacuum oven at 25°C for about 88 hours. 4,6-Dichloro-5-(2,2-diethoxyethyl)pyrimidine was obtained as an amber colored oil (670 g, 96% yield).1H NMR (300 MHz, d6-DMSO) δ 8.82-8.71 (m, 1H), 3.60 (dq, J = 9.6,7.0 Hz, 2H), 3.39 (dq, J = 9.6,7.0 Hz, 2H ), 3.13 (dd, J = 5.6,3.1Hz, 2H), 1.00 (dd, J = 8.1,6.0Hz, 6H).